Role of metallothionein in lung inflammation induced by ozone exposure in mice.
Metallothionein (MT) is a free radical scavenger induced by inflammatory stimuli; however, its roles in inflammation have not been fully investigated. In the present study, we genetically determined the role of MT in ozone (O(3))-induced lung inflammation using MT-I/II null (-/-) mice. Subacute (65 h) exposure to O(3) (0.3 ppm) induced lung inflammation and enhanced vascular permeability, which was significantly greater in MT(-/-) than in corresponding wild-type mice. Electron microscopically, O(3) exposure induced vacuolar degeneration of pulmonary endothelial and epithelial cells, and interstitial edema with focal loss of the basement membrane, which was more prominent in MT(-/-) than in wild-type mice. O(3) -induced lung expression of interleukin-6 was significantly greater in MT(-/-) than in wild-type mice; however, lung expression of the chemokines examined was comparable in both genotypes of mice in the presence of O(3). Following O(3) exposure, the formation of oxidative stress-related molecules/adducts, such as heme oxidase-1, inducible nitric oxide synthase, 8-hydroxy-2'-deoxyguanosine, and nitrotyrosine, in the lung was significantly greater in MT(-/-) than in wild-type mice. Collectively, MT protects against O(3)-induced lung inflammation, at least partly, via the regulation of pulmonary endothelial and epithelial integrity and its antioxidative property.
Inoue
Ken-ichiro
K
Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Japan. inoue.kenichirou@nies.go.jp
Takano
Hirohisa
H
Kaewamatawong
Theerayuth
T
Shimada
Akinori
A
Suzuki
Junko
J
Yanagisawa
Rie
R
Tasaka
Sadatomo
S
Ishizaka
Akitoshi
A
Satoh
Masahiko
M
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010083:Oxidants, Photochemical / Q000008:administration & dosage / Q000633:toxicity*; D010126:Ozone / Q000008:administration & dosage / Q000633:toxicity*; D011014:Pneumonia / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012129:Respiratory Function Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides; C491054:Mt2 protein, mouse; D010083:Oxidants, Photochemical; D012333:RNA, Messenger; C525355:metallothionein-1, mouse; D010126:Ozone; D008668:Metallothionein; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1